Improving Cardiovascular Health Through Personalized Treatment

EVIDENCE BASED INSIGHT

Cardioprotective Dialysis: Improving Cardiovascular Health Through More Personalized Treatment

September 21, 2020 • 6 min read

BERNARD CANAUD, MD, PhD • ALLAN COLLINS, MD, FACP


By taking a more personalized approach to renal replacement therapy (RRT), it is possible to reduce the very high incidence of cardiovascular disease and death among kidney disease patients. Specific strategies include thorough cardiac screening and risk assessment, evaluation of individual lifestyle factors, consideration of various treatment options such as home-based therapies, and ongoing attention to the manageable complications of dialysis. Detecting and controlling fluid overload and hypertension, cardiac arrhythmia, cardiac remodeling, and vascular calcification can significantly improve the cardiovascular health of individual patients.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients.1 CVD is highly prevalent in 30 to 50 percent of late-stage CKD patients starting dialysis and steadily increases up to 60 to 70 percent of CKD patients on maintenance dialysis.2,3 From a pathophysiological perspective, 60 to 80 percent of CKD patients at stage 5 begin dialysis, or renal replacement therapy (RRT), with hypertension and fluid overload, major risk factors for cardiac disease.4,5,6 The percentage remains between 30 and 70 percent in prevalent stabilized dialysis patients (Figure 1).3,7,8,9,10,11 Furthermore, the relative risk of death from cardiovascular events is between 10 and 30 times higher in late-stage CKD population compared with the general population.12,13
 

Figure 1 | Pathophysiological mechanisms involved in uremic cardiomyopathy development

CVD should not be considered as an intractable fatality of CKD patients but rather should encourage exploration of solutions to efficiently fight this plague.14 CVD results from multiple factors that may be  classified as non-modifiable or modifiable.15,16 Nonmodifiable factors include age, gender, ethnicity, genetics, and comorbid condition. Modifiable factors include dialysis option, treatment schedule and protocol, practice patterns, quality care management, and lifestyle-related factors such as diet, environment, and treatment observance.

IMPROVING CARDIAC OUTCOMES IN HEMODIALYSIS PATIENTS: THE TOP FIVE ESSENTIALS

Modifiable CVD factors can be addressed through RRT that focuses on five common manageable complications: correcting fluid overload and hypertension, detecting and preventing cardiac arrhythmia, reversing cardiac remodeling, detecting and preventing vascular calcification, and adjusting RRT to patient risk stratification (Figure 2, Figure 3).17

Figure 2 | Five essential actions to reduce cardiac mortality in CKD5 dialysis patients

Figure 3 | Goal-oriented patient care

CORRECTING SODIUM EXCESS, VOLUME OVERLOAD, AND HYPERTENSION

Extra-cellular fluid overload (FO) is a major source of morbidity of hemodialysis (HD) patients. In a retrospective cohort study using US Renal Data System data, it has been shown that severe fluid overload, such as pulmonary edema and congestive heart failure, is a significant cause of hospital admission and 30-day re-admission.18 This observation suggests that fluid volume is not adequately managed in maintenance HD patients, worsening during the transition period from the hospital to the dialysis unit. Interestingly, according to a 2004 Dialysis Outcomes and Practice Patterns Study (DOPPS) report including 16,720 prevalent HD patients (1996-2002), 46 percent of United States and 25 percent of HD patients present with congestive heart failure suggesting exposure to chronic FO.19 Long-term exposure to FO and hypertension trigger cardiac remodeling, contributing to heart failure in dialysis patients.21,22 This kidney/cardiac cross-talk has been identified as a typical example of a self-aggravating process.22

Restoring sodium mass balance, volume, and blood pressure control are critical to minimizing dialysis patient cardiac risk. A comprehensive, precise approach to managing fluid volume and hemodynamic status of dialysis patients should rely on a four-step approach, with specific adaptations according to dialysis modality.33,34

  1. Adjust dry weight probing and dialysis treatment prescription.32,35
  2. Manage instrumentation and/or imaging.36,37,38
  3. Track cardiac biomarkers CA125, BNP, NT-proBNP, copeptin, and troponin I or T.39,40,41,42,43,44
  4. Introduce machine learning algorithms to support physician, patient, and caregiver decision making.45,46,47


DETECTING AND PREVENTING CARDIAC ARRHYTHMIA AND SUDDEN CARDIAC DEATH

Cardiac arrhythmia (CA) and sudden cardiac death (SCD) account for 26.9 percent of mortality in CKD5 HD patients.2 Although CKD patients are at increased risk for arrhythmias, the underlying mechanisms of CA and their association with SCD are not completely understood.48,49 Several explanations have been proposed, but they are likely facilitated by cardiac structural changes. CKD5 HD patients often present with a histopathology referred to as “uremic cardiomyopathy,” a finding that includes varying degrees of left ventricular hypertrophy and dilation, systolic and diastolic dysfunction, and fibrosis—which predispose the patient to arrhythmias.

Intermittent HD treatments may also trigger arrhythmias through the interaction of cardiac ischemia and electrolyte shifts. Additional factors may be implicated such as profound anemia, hypoxemia, and clearance of cardiac medications. Comparatively, the risk of triggering arrhythmia during PD is reduced and may offer a therapeutic alternative for arrhythmic-prone patients.

Clinically significant arrhythmias are common in HD patients, and bradycardia and asystole—rather than ventricular tachycardia—may be key causes of sudden death in HD patients. Dialysis practices have a strong impact on incidence, type, and severity of arrhythmias. Therefore, new treatment approaches to prevent arrhythmias and SCD are critical.

REVERSING CARDIAC REMODELING

Cardiac remodeling is a strong determinant of cardiac outcome, including heart failure, arrhythmias, and sudden death in CKD5 HD patients, resulting mainly from hemodynamic load (fluid overload, hypertension) and unload (fluid depletion, ischemic injury) imposed by intermittent HD.61,62 Cardiac remodeling may also be influenced by:

  • Uremic toxins and uremic milieu, such as FGF23, PTH, oxidative stress, and inflammation.
  • Neurohormonal activation and other factors involved in treatment of dialysis patients, including access flow rate, anemia, iron status, and ESA.63,64,65,66,67

Other factors unrelated to remodeling may also affect cardiac structure and influence the course of heart disease, including ischemic heart disease, arrhythmias, and valvular disease.

Slowing or reversing cardiac remodeling should be a priority goal in dialysis patient heart management.63,68 In this context, three complementary approaches to systematically modulate cardiac remodeling may prove beneficial: mechanical, pharmacological, and biological interventions. 

Mechanical intervention relies on a strict control of both volume and pressure, a “volume first” policy.69 Pharmacological intervention introduces the use of cardiac agents—such as betaadrenergic blockers, ACE inhibitors, AR blockers, and aldosterone antagonists—when fluid volume and pressure are corrected.26,68,70 These cardiac agents may provide additional benefits by slowing or reversing cardiac structure abnormalities and by improving hemodynamic function. Biological intervention focuses on improving tolerance and enhancing RRT modality efficiency by revisiting treatment options, schedule, and time.71,72,73

Precise cardiac management of CKD5 dialysis patients should be performed in close collaboration with a cardiology team in conjunction with cardiac monitoring and biomarkers.

DETECTING AND PREVENTING VASCULAR AND VALVULAR CALCIFICATION

Vascular and valvular calcifications are major risk factors for CKD5 dialysis patients. Arterial medial calcification is responsible for increased vascular stiffness, while arterial intima calcification facilitates plaque rupture.74,75 Valvular calcification is responsible for aortic stenosis.76 Calcification modifies cardiac structure and functionality, resulting in heart failure. Vascular calcification is an active, complex process caused by uremic bone metabolic disorders, regulatory failure of the calcificationinhibitory system, and active phenotypic change in vascular smooth muscle cells (VSMCs) into osteoblast-like cells.77,78 Monitoring vascular calcification process or risk should be part of best clinical practices.

Several therapeutic interventions have shown interesting results in delaying vascular calcification. They include introducing noncalcium-containing phosphate binders, low-dose active vitamin D, and calcimimetics; supplementing magnesium; enhancing RRT efficiency; and adjusting dialysate composition.83 Delaying or reducing vascular calcification is feasible by combining several approaches; however, questions remain about if these risk reduction measures correlate with better cardiac outcomes for dialysis patients; further studies are necessary.

CUSTOMIZING RRT: PATIENT RISK, PREFERENCE, AND PERCEPTION

RRT must trend away from “one size fits all” to a more personalized and customized approach.84 In other words, dialysis treatment should fit patient needs, patient risk, and patient perception rather than the reverse as it is currently applied. This is the clinical meaning of patient-centered care. In that perspective, choice of dialysis modality should result from shared decision making involving patient, physician, and main stakeholders where various treatment options are discussed in terms of benefits and risks.85 Ultimately, the nephrologist will identify patient medical risks, evaluate personal motivations and feasibility, as well as assess individual capabilities for self-care treatment.86

Cardiac risk screening and profile stratification are paramount best clinical practices in managing dialysis patients. A baseline cardiovascular screening should be performed upon initiation of dialysis, with regular annual screenings scheduled to monitor changes in cardiac structure, carotid and supra aortic arteries, thoracic and abdominal aorta, and peripheral arterial limbs.87 A more precise cardiac assessment relying on cardiac structural and functional characteristics is required for dialysis patients suitability, including electrocardiography, echocardiography, vascular calcification score or pulse wave velocity, and cardiac biomarkers.88 Depending on the specific patient risk and baseline cardiac screening, additional cardiac explorations might be indicated.

Based on patient assessment and shared decision-making processes, a personalized dialysis modality suited to patient expectations might be identified with a high degree of success. Several studies have shown that empowering patients enhances their trust and consequently facilitates the use of self-treatment options, increases treatment adherence, and improves outcomes.86,102,103,104 Furthermore, it is commonly recognized that more frequent dialysis, longer treatment time, specific modalities, or home-based therapies may further improve patient perception and cardiac outcomes.89 RRT customization and adjustment should include patient-centered goals and experience as quality care indicators.17,84,90,91

The nephrology team continues to be responsible for regularly monitoring dialysis treatment performances and tolerance, revising and readjusting prescription and modality as medically necessary. In brief, the shared decision process and patient empowerment may enhance RRT value with a higher quality of life by improving outcomes. Rapidly expanding technological tools—including digital medicine, connected devices, and the support of artificial intelligence—have demonstrated additional means to improve patient outcomes by providing reliable quality control tools for care teams.92 New metrics focused on patient needs, such as patient-reported outcome measures (PROM) or patient-reported experience measures (PREM), will further enrich the panel of clinical performance measures. Several recent studies have shown the strong predictive value of PROM tools, particularly when they are digitally supported or web based.93,94,95

Cardiac burden should not be considered as an intractable fatality of advanced CKD patients on maintenance renal replacement therapy (PD, HD, kidney transplant), but rather should encourage exploration of effective RRT solutions to halt this frustrating and devastating process.96,97,98,99,100,101 Through customized, personalized RRT, it is possible to not only address CKD-CVD but also manage patient risk, preference, and perception for every patient, every day.

Meet The Experts

BERNARD CANAUD, MD, PhD

Senior Chief Scientist, Fresenius Medical Care

ALLAN J. COLLINS, MD, FACP

Senior Chief Scientist, Fresenius Medical Care

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